NAD+ and MOTS-c are often compared because both are tied to cellular energy and aging. NAD+ (nicotinamide adenine dinucleotide) is an essential coenzyme, not a peptide, that the body makes from dietary precursors. MOTS-c is a peptide encoded in mitochondrial DNA, studied as a metabolic regulator. Neither is an FDA-approved treatment.
At a glance
| NAD+ | MOTS-c | |
|---|---|---|
| What it is | Essential coenzyme (not a peptide) involved in cellular energy production and DNA repair, made by the body from dietary precursors | Peptide encoded in mitochondrial DNA, studied as a metabolic regulator and sometimes called an exercise mimetic |
| How it's thought to work | Cofactor for sirtuins (SIRT1 to SIRT7), proteins involved in DNA repair and energy metabolism; levels are described as declining with age | Studied for moving to the cell nucleus under metabolic stress and activating AMPK signaling, affecting glucose and fat metabolism |
| Regulatory status | Injectable NAD+ is not an FDA-approved treatment | Not FDA-approved for any human use |
| Strength of evidence | Aging research is mostly in animals and labs; a small 2019 human pilot study measured how infused NAD+ is processed | Insulin-sensitivity and exercise findings come from animal studies; human research is at an early stage |
| Reported side effects | Flushing (warmth and discomfort) that typically passes within 15 to 30 minutes; nausea | Injection site reactions; long-term human data is limited |
| Common vial sizes | 100mg, 500mg, 1000mg | 5mg, 10mg |
| Mixing math example | 500 mg + 5 mL BAC water = 100,000 mcg/mL, 1 mg per unit | 10 mg + 2 mL BAC water = 5,000 mcg/mL, 50 mcg per unit |
Key differences
NAD+ acts as a cofactor for sirtuins (SIRT1 to SIRT7), proteins involved in DNA repair, mitochondrial function and energy metabolism. MOTS-c is studied for moving to the cell nucleus under metabolic stress and activating AMPK signaling, affecting glucose use and fat metabolism.
Both are described as declining with age: NAD+ levels are described as falling with age, and declining MOTS-c levels have been observed to correlate with aging.
NAD+ has a distinctive reported side effect, flushing that can feel intense and typically passes within 15 to 30 minutes, along with nausea. MOTS-c's reported side effects are injection site reactions.
What the research covers
Most NAD+ aging research is in laboratory and animal models; human research on directly administered NAD+ is small, including a 2019 pilot study of how infused NAD+ is processed. MOTS-c's findings on insulin sensitivity and exercise capacity come from animal studies, and human research is at an early stage.
Sources
- A Pilot Study Investigating Changes in the Human Plasma and Urine NAD+ Metabolome During a 6 Hour Intravenous Infusion of NAD+. Grant R et al. Frontiers in Aging Neuroscience, 2019. Human trial
- NAD+ in aging, metabolism, and neurodegeneration. Verdin E et al. Science, 2015. Review
- The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Lee C et al. Cell Metabolism, 2015. Preclinical
- MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Reynolds JC et al. Nature Communications, 2021. Human trial
Frequently asked questions
What is the difference between NAD+ and MOTS-c?
NAD+ is a coenzyme that acts as a cofactor for sirtuins. MOTS-c is a mitochondrial-encoded peptide studied for activating AMPK signaling.
Is NAD+ a peptide?
No. NAD+ is a coenzyme, not a peptide, though it is commonly discussed alongside peptides. MOTS-c is a peptide.
Is NAD+ or MOTS-c FDA-approved?
Injectable NAD+ is not an FDA-approved treatment, and MOTS-c is not FDA-approved for any human use.
Is there human research on NAD+ or MOTS-c?
Human research is early for both. NAD+ has a small 2019 pilot study of infused NAD+, and MOTS-c findings come mainly from animal studies.
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